Safety and Immunogenicity of 10-valent and 13-valent Pneumococcal Conjugate Vaccines in Papua New Guinean Children

Phase 3

• Conditions: Meningitis; Otitis Media; Sepsis; Pneumonia; Bacteraemia
• Interventions: Biological: Prevenar 13 and Synflorix

• Registration Number: NCT01619462
• Lead Sponsor: Papua New Guinea Institute of Medical Research

Brief Summary

The study aims to evaluate the safety and immunogenicity of the 10-valent and 13-valent pneumococcal conjugate vaccines when administered in an accelerated schedule in Papua New Guinean children, who experience early dense upper respiratory tract colonisation with a broad range of pneumococcal serotypes, and to compare antibody titres following a booster dose of polysaccharide vaccine at 9 months with those children who received no booster at the same age.

Detailed Description

The primary aim of the study is to determine whether PCV10 and PCV13 are safe and immunogenic in PNG infants for the serotypes in the respective vaccines. This study is important for the following reasons:

1. There is a lack of data worldwide on immunogenicity in populations with very high early onset of dense URT carriage.

2. The EPI immunisation schedule is very accelerated in PNG (ages 1,2 and 3 months).

3. There are not data on functional antibody to PCVs in PNG.

4. There are no data on NTHi Protein D antibody responses in PNG and worldwide in population with very high URT carriage rates from a young age, i.e. those most likely to benefit from a vaccine including NTHi protein carrier.

5. It is important to investigate impact of vaccine on carriage density in view of our finding of limited impact of 7vPCV on URT carriage.

6. There is no data on antibody responses following 10v or 13v PCV to booster with PPV as young as 9 months of age (which would be the most appropriate within the current PNG EPI schedule and in the many other third world countries).

7. There is no data on antibody responses (including functional assays) to 23vPPV challenge at age 2 years after 23vPPV booster at age 9 months in children primed with PCV.

8. The broad range of serotypes causing IPD in PNG necessitates continuing consideration of 23vPPV as a potential booster at age 9 months.

9. Serotype-specific B cell memory is an important aspect that we can now test to address immunological safety of PPV in children primed with PCV.

10. The Global Alliance for Vaccines and Immunisation (GAVI) and the World Health Organisation (WHO) have committed to the introduction of PCV for infants in GAVI-eligible countries (including PNG) using novel funding mechanism. In PNG, the introduction of a PCV is planned for 2013.

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2012-05-28
• Study First Submitted QC: 2012-06-12
• Study First Posted: 2012-06-14
• Status Verified: 2012-09
• Last Update Submitted: 2014-03-20
• Last Update Posted: 2014-03-21
• Primary Completion: 2014-04
• Study Completion: 2016-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Health infants between 28 - 35 days old

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Exclusion Criteria

• Infants of women not intending to remain in the are for at least two years
• Birth weigh < 2000 g (2kg)
• Severe congenital abnormalities
• Mother or child known to be HIV positive

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Synflorix or PCV10	Prevenar 13 and Synflorix	130 children will receive Synflorix at 1-2-3 months
Prevenar 13	Prevenar 13 and Synflorix	130 children will receive Prevenar 13 at 1-2-3 months

Primary Outcome Measures

Name	Time	Method
Proportion of children with serotype-specific IgG concentration >= 0.35ug/ml at 4 and 9 months of age for 90% of PCV vaccine serotypes and proportion of children with OPA >=1:8 titres at 4, 10 and 24 months	3 years	IgG concentration to vaccine serotypes are \>= 0.35ug/ml post-dose 3 at 4 and 9 months. Serotype-specific IgG concentration \>=0.35ug/ml is protective level against invasive pneumococcal diseases. Opsonophagocytic titre of \>=1:8 examined at 4, 10 and 24 months will inform on functional antibodies induced by vaccination.

Secondary Outcome Measures

Name	Time	Method
Determine rates of hospital admission for acute respiratory tract infections at 9 and 23 months	2 yrs	Admissions and morbidity for acute respiratory tract infections will be documented at 9 and 23 months.
Compare antibody concentrations to pneumococcal and Haemophilus influenzae protein antigens.	2 years	Measure antibody titres to surface proteins of pneumococci and Hi including Hi protein D, the carrier protein in PCV10 (Synflorix).
Determine carriage rates and bacterial load of pneumococci and H.influenzae	3 years	Proportion of carriage before and after vaccination will be measured using conventional culture methods. Bacterial load will be measured using PCR to determine impact of vaccines

Trial Locations

Locations (1)

Papua New Guinea Institute of Medical Research; 🇵🇬 Goroka, Eastern Highlands Province, Papua New Guinea